Abuse Potential of Intravenous Oxycodone/Naloxone Solution in Nondependent Recreational Drug Users

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Background and Objective

Abuse of opioid analgesics has become a public health issue. Some opioid abusers use intravenous administration to increase the magnitude of positive reinforcing effects. Intravenous co-administration of oxycodone with naloxone, an opioid antagonist, may reduce these rewarding effects and discourage abuse. A 2:1 oxycodone:naloxone (OXN) tablet formulation has been studied in the USA for the management of moderate-tosevere chronic pain. Intravenous administration of a 2:1 oxycodone:naloxone solution (sOXN) reflects the oxycodone: naloxone ratio found in laboratory studies of OXN following tampering for intravenous administration. The objective of this study was to characterize abuse-deterrent properties of sOXN.


This single-center, double-blind, randomized, placebo-controlled, active-controlled, crossover study enrolled nondependent recreational opioid users with experience using multiple (two or more) routes of administration. Following demonstration that subjects could discern between placebo and oxycodone, 24 eligible male and female subjects were randomized to receive intravenous injections of 0.07 mg/kg oxycodone (OXY), 0.07 mg/kg oxycodone and 0.035 mg/kg naloxone solution (sOXN), or matching placebo over three visits. Pharmacokinetics, pharmacodynamics, safety, and tolerability were assessed at scheduled times up to 8 h post-dose. Parameters were computed and statistically compared among treatments. Results Pharmacokinetics were similar between OXY and sOXN. Subjects reported significantly fewer rewarding effects with sOXN compared with OXY; differences between sOXN and placebo were generally not significant. sOXN was well tolerated.


Significant reductions in drug liking and other subjective effects following administration of sOXN compared with OXY indicate that naloxone concentrations were sufficient to antagonize the effects of oxycodone when abused by the intravenous route of administration in opioid-experienced drug users.

Key Points

Significant reductions in the degree of drug liking and other pharmacodynamic effects following intravenous administration of oxycodone/naloxone compared with oxycodone were consistent with the agonist-antagonist interaction hypothesis.

Key Points

Naloxone concentrations were sufficient to antagonize the reinforcing effects of oxycodone when abused by the intravenous route of administration in opioid-experienced drug users.

Key Points

Drug liking reduction by intravenous administration of oxycodone/naloxone observed in this study may not represent the situation in the real-world settings.

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